To ascertain the tolerance mechanisms of aquatic organisms to arti cial chemicals, intergenerational sensitivity changes of Chironomus yoshimatsui to a carbamate pesticide (pirimicarb) and pharmaceutical chemical (diazepam) were investigated. The larvae (< 48-h-old) in each generation were exposed to both chemicals for 48 h and then the surviving chironomids were cultured until the fth generation (F0-F4) without chemical addition. The 48-h 50% effective concentration (EC 50 ) value of chironomids was determined for each generation. In the pirimicarb treatment group, the EC 50 values signi cantly increased in F3 and F4, and those in the diazepam treatment group slightly increased. Catalase, Cytochrome P450 and hemoglobin (Hb) mRNA levels were monitored to see whether these were related to the trans-generational sensitivity. Although the generalized linear model results showed that the sensitivity to diazepam was slightly increased in the diazepam treatment, we could not nd any mRNA levels related to sensitivity alteration. In contrast, the model approach showed that the chironomids exposed to pirimicarb trans-generationally became tolerant with increasing Hb mRNA levels. Therefore, they might decrease their oxidative chemical stress by modifying Hb gene transcription.